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welcome to medical breakthroughs from Penn Medicine, advancing medicine through precision diagnostics and novel therapies. Here's your host, Dr Charles Turk, while messenger RNA or mRNA, is nothing new, using it to provoke an immune response in order to combat Covid 19 is a novel strategy. So today we'll be exploring the nuances, benefits and safety of M RNA vaccine technology in tackling the coronavirus. Welcome to medical breakthroughs from Penn Medicine on reach, MD. I'm Dr Charles Turk in joining me to discuss covid 19 vaccine technology Is Dr Drew Weisman, professor of medicine at Penn Medicine. Dr. Weisman, welcome to the program. Thank you very much, Dr Weissman. Let's dive right in. Would you explain mRNA technology for us? Did you ever think that your research in that area would be leading the charge against a global pandemic? So let me start with what RNA is our genome. Our DNA contains all of the proteins and all of the instructions that makes ourselves grow and makes us live. In order to get those instructions into a protein production, the cell uses an RNA, and what the RNA does is it makes a copy of the sequence of the protein in the DNA that's then read by a machine that produces the protein. So the mRNA technology is kind of the middleman. When you deliver it to a cell, it immediately is read by those machines and produces protein. In the case of Covid, that protein is put on the surface of a cell, and the immune system recognizes it as foreign and makes a response against it. Katie Carrico and I started studying mRNA over 20 years ago. We discovered nucleoside modified mRNA. That's the form of RNA that's used in both the Moderna and Pfizer vaccines. And what's different about it is that RNA Therapeutics didn't go anywhere because the RNA was so inflammatory it made animals sick. When you injected it, Katie and I developed modified RNA that doesn't induce an inflammatory response, and that made it much safer and much better for a vaccine digging a bit deeper here. Dr. Weissman, what is the relationship between M. R. N A. And the immune system? There's quite a few, so RNA has been studied as a vaccine for almost 30 years in many different formats. The one that we're using, along with Modern and Pfizer, was developed about seven years ago, we started to investigate RNA vaccines, and there's a lot of important characteristics. So the first is that the RNA is modified to get rid of the inflammation. It's also highly purified to get rid of contaminants that could interfere. It's then put into what's called a lipid nanoparticle. It's essentially a fat droplets that both protects the RNA, but most importantly, gives an adjuvant activity. So an adjuvant helps stimulate an immune response in a vaccine. But it's a highly specialist adjuvant. It specifically drives anybody production. And that's why we see such high levels of anybody produced by this vaccine like to talk about another facet of vaccine technology. How is an RNA based vaccine different than, let's say, the flu vaccine? Most flu vaccines are inactivated viruses, so what that means is that they take the flu virus that grow it up in eggs and then inactivated with a chemical. What that does is it presents the body, the virus, so the entire virus. But the virus is not infectious. The immune system responds to all of the proteins in that virus. With RNA, we're only giving a single protein. The spike protein from Covid, so there's no chance of getting an infection from the RNA vaccine because it's one out of hundreds of proteins that could be present in the virus. The RNA also has better ABS, even activity, and for the most part is superior to most inactivated vaccines. For those just tuning in, you're listening to medical breakthroughs from Penn Medicine Enrich, MD. I'm Dr Charles Turk, and I'm speaking with Dr Drew Weissman about using mRNA vaccine technology to combat covid 19. Dr. Weissman, what would you say to those who may question the safety and efficacy of this vaccine technology? I understand why they're nervous. They've never heard of this vaccine platform before, and 11 months ago it was first being developed for Covid 19. The reason why people haven't heard about it is because it's been in research hands up until then. But it's been studied for over eight years, clinical trial, so actually giving similar vaccines. The people have been going on for over five years, so this isn't brand new technology. It's well established, well understood technology. The big difference is we had a pandemic emergency, and this platform allows for rapid development and that's what happened. And as we now know, there are new variants of the SARS cov two virus spreading rapidly. How will that impact both the vaccines that have already been rolled out worldwide and vaccines currently in development? So the new variants are an enormous concern to everybody and what you hear about all of these variants so that they spread better. That means the virus is learning how to infect people better. The concern is that any changes that occur might make vaccines not work as well. That's only really been a concern with the South African strain that has shown a reduction in neutralizing so ability to protect against that virus. With current vaccines. With the RNA, vaccine is easy to fix and both Moderna Advisor are currently working on this. You simply have to put the new variants into the RNA vaccine, and you'll likely or very likely, get coverage of the new variants in the long term. It's really as long as we haven't vaccinated the world, new variants are going to keep appearing, and we're always going to have to worry. Are one of these new variants not sensitive to a vaccine, So the faster we can vaccinate the world, the sooner we get rid of these variants popping up. Finally, Dr Weissman, looking ahead to the next 15 years, what other therapeutic avenues do you foresee for mRNA technology? My lab has been working on modified RNA for 15 years. We have many new therapeutics that we're developing. We have over 30 different vaccines in animal studies. Five of them are going into human clinical trials. Soon we also have other therapies were delivering monoclonal antibodies with mRNA were also modifying and editing the genome with RNA. And we're doing that by encoding enzymes that allow gene editing. MRNA itself in the vaccine does not change. DNA doesn't alter DNA, but by using tricks to encode proteins that edit DNA, we're hoping to be able to cure diseases like sickle cell anemia, immune deficiencies and others with a single injection of r n A l N P s. Thank you so much for providing some great perspective on the future of M RNA technology. And with that in mind, I want to thank my guest Dr Weissman, for joining me to discuss M RNA vaccine technology and fighting covid 19. Dr. Weissman, it was great having you on the program. Thank you very much. You've been listening to medical breakthroughs from Penn Medicine to download this podcast or to access others in the series, please visit Reach MD com slash pen and visit Penn Medicine, referring Provider Resources, an exclusive program that helps referring physicians connect with PEN. Here, you can find education resources, information about our expedited referral process and communication tools. To learn more, visit www dot penn medicine dot org slash four Dash Health Dash Care Dash Professionals Thank you for listening.
March 11, 2021